TRPA1 在免疫細(xì)胞中的表達(dá)和病理生理學(xué)

The non-selective cation channel TRPA1 is best known as a broadly-tuned sensor expressed in nociceptive neurons, where it plays key functions in chemo-, thermo-, and mechano-sensing. However, in this review we illustrate how this channel is expressed also in cells of the immune system. TRPA1 has been detected, mainly with biochemical techniques, in eosinophils, mast cells, macrophages, dendritic cells, T cells, and B cells, but not in neutrophils. Functional measurements, in contrast, remain very scarce. No studies have been reported in basophils and NK cells. TRPA1 in immune cells has been linked to arthritis (neutrophils), anaphylaxis and atopic dermatitis (mast cells), atherosclerosis, renal injury, cardiac hypertrophy and inflammatory bowel disease (macrophages), and colitis (T cells). The contribution of TRPA1 to immunity is dual: as detector of cell stress, tissue injury, and exogenous noxious stimuli it leads to defensive responses, but in conditions of aberrant regulation it contributes to the exacerbation of inflammatory conditions. Future studies should aim at characterizing the functional properties of TRPA1 in immune cells, an essential step in understanding its roles in inflammation and its potential as therapeutic target.

離心管

非選擇性陽(yáng)離子通道 TRPA1 最為人所知的是在傷害感受神經(jīng)元中表達(dá)的廣泛調(diào)諧的傳感器，它在化學(xué)、熱和機(jī)械傳感中發(fā)揮關(guān)鍵作用。然而，在這篇綜述中，我們說(shuō)明了這個(gè)通道是如何在免疫系統(tǒng)細(xì)胞中表達(dá)的。已在嗜酸性粒細(xì)胞、肥大細(xì)胞、巨噬細(xì)胞、樹突細(xì)胞、T 細(xì)胞和 B 細(xì)胞中檢測(cè)到 TRPA1，主要是通過(guò)生化技術(shù)，但未在中性粒細(xì)胞中檢測(cè)到。相比之下，功能測(cè)量仍然非常稀缺。沒有關(guān)于嗜堿性粒細(xì)胞和 NK 細(xì)胞的研究報(bào)告。免疫細(xì)胞中的 TRPA1 與關(guān)節(jié)炎（中性粒細(xì)胞）、過(guò)敏反應(yīng)和特應(yīng)性皮炎（肥大細(xì)胞）、動(dòng)脈粥樣硬化、腎損傷、心臟肥大和炎癥性腸病（巨噬細(xì)胞）以及結(jié)腸炎（T 細(xì)胞）有關(guān)。TRPA1 對(duì)免疫的貢獻(xiàn)是雙重的：作為細(xì)胞應(yīng)激、組織損傷和外源性有害刺激的檢測(cè)器，它會(huì)導(dǎo)致防御反應(yīng)，但在異常調(diào)節(jié)的情況下，它會(huì)導(dǎo)致炎癥惡化。未來(lái)的研究應(yīng)旨在表征免疫細(xì)胞中 TRPA1 的功能特性，這是了解其在炎癥中的作用及其作為治療靶點(diǎn)的潛力的重要一步。

T75細(xì)胞培養(yǎng)瓶

The immune system is a highly adaptable and versatile system capable of recognizing a wide range of pathogens, ranging from the smallest virus to the largest tapeworm.It consists of two interconnected branches: the innate and the adaptive immune system.The innate immune system is the first line of defense and is responsible for the fast, nonspecific, initial immune response. In addition to the defense mechanisms relying on barrier and clearance functions, which are mainly based on the activities of epithelial cells,the innate immunity is based on multiple cell types, including eosinophils, neutrophils,mast cells, innate lymphoid cells, macrophages, natural killer (NK) cells, and basophils(Figure 1). Sometimes, the innate immune system is capable of eliminating the pathogenby itself, but in other cases the adaptive immune system steps in. Dendritic cells link the two systems by detecting antigens and presenting them to T cells. The adaptive immune system, based on T and B cells, has a slower activation mechanism (5–6 days), but has a more targeted approach, tailored by the identity of the intruder. The proper activation and propagation of an immune reaction requires a balance between pro- and anti-inflam matory mediators. Disruption of this balance leads to the survival of the pathogen and/or the destruction of collateral healthy tissue.

免疫系統(tǒng)是一個(gè)適應(yīng)性強(qiáng)、用途廣泛的系統(tǒng)，能夠識(shí)別從最小的病毒到最大的絳蟲等各種病原體。它由兩個(gè)相互關(guān)聯(lián)的分支組成:先天免疫系統(tǒng)和適應(yīng)性免疫系統(tǒng)。先天免疫系統(tǒng)是第一道防線，負(fù)責(zé)快速、非特異性的初始免疫反應(yīng)。除了依賴barrier的防御機(jī)制和主要基于上皮細(xì)胞活動(dòng)的清除功能外，先天免疫基于多種細(xì)胞類型，包括嗜酸性粒細(xì)胞，中性粒細(xì)胞，肥大細(xì)胞、先天淋巴細(xì)胞、巨噬細(xì)胞、自然殺傷細(xì)胞和嗜堿性細(xì)胞有時(shí)，先天免疫系統(tǒng)能夠消滅病原體但在其他情況下，適應(yīng)性免疫系統(tǒng)會(huì)介入。樹突細(xì)胞連接通過(guò)檢測(cè)抗原并將它們呈遞給T細(xì)胞，自適應(yīng)免疫以T細(xì)胞和B細(xì)胞為基礎(chǔ)的免疫系統(tǒng)具有較慢的激活機(jī)制(5-6天)更有針對(duì)性的方法，根據(jù)入侵者的身份量身定制。適當(dāng)?shù)募せ蠲庖叻磻?yīng)的傳播需要在促炎和抗炎之間取得平衡炎癥介質(zhì)。這種平衡的破壞會(huì)導(dǎo)致病原體的存活和/或側(cè)枝健康組織的破壞。